Iron-regulatory proteins: molecular biology and pathophysiological implications

Iron is required for key cellular functions, and there is a strong link between iron metabolism and important metabolic processes, such as cell growth, apoptosis and inflammation. Diseases that are directly or indirectly related to iron metabolism represent major health problems. Iron-regulatory proteins (IRPs) 1 and 2 are key controllers of vertebrate iron metabolism and post-transcriptionally regulate expression of the major iron homeostasis genes. Here we discuss how dysregulation of the IRP system can result from both iron-related and unrelated effectors and explain how this can have important pathological consequences in several human disorders

Ironing out Macrophage Immunometabolism

Over the last decade, increasing evidence has reinforced the key role of metabolic reprogramming in macrophage activation. In addition to supporting the specific immune response of different subsets of macrophages, intracellular metabolic pathways also directly control the specialized effector functions of immune cells. In this context, iron metabolism has been recognized as an important component of macrophage plasticity. Since macrophages control the availability of this essential metal, changes in the expression of genes coding for the major proteins of iron metabolism may result in different iron availability for the macrophage itself and for other cells in the microenvironment. In this review, we discuss how macrophage iron can also play a role in immunometabolism

New perspectives on the molecular basis of the interaction between oxygen homeostasis and iron metabolism

Oxygen and iron are two elements closely related from a (bio)chemical point of view. Moreover, they share the characteristic of being indispensable for life, while also being potentially toxic. Therefore, their level is strictly monitored, and sophisticated pathways have evolved to face variations in either element. In addition, the expression of proteins involved in iron and oxygen metabolism is mainly controlled by a complex interplay of proteins that sense both iron levels and oxygen availability (ie, prolyl hydroxylases, hypoxia inducible factors, and iron regulatory proteins), and in turn activate feedback mechanisms to re-establish homeostasis. In this review, we describe how cells and organisms utilize these intricate networks to regulate responses to changes in oxygen and iron levels. We also explore the role of these pathways in some pathophysiological settings

Il caso dello sceneggiato televisivo "I fratelli Karamazov": il "cristianesimo sofferto" di Diego Fabbri nella Rai pedagogica dell'era bernabeiana

Il contributo si propone di indagare il profondo legame di Diego Fabbri con l’opera di Dostoevskij che influenza la saggistica, la drammaturgia e l’impegno istituzionale dello sceneggiatore forlivese presso il Centro Cattolico Cinematografico (CCC). In particolare, si mira a definire il contributo personale di Fabbri negli sceneggiati Rai I fratelli Karamazov (1969) e I demoni (1972), in cui l’autore porta sullo schermo anni di studio e riflessione sull’opera dostoevskiana. Per meglio comprendere la relazione che corre tra la sceneggiatura, la produzione e la regia di Sandro Bolchi si analizza infine nel dettaglio il caso de I fratelli Karamazov.The essay aims to investigate Diego Fabbri’s strong connection to Dostoyevsky’s work, which influenced the writer’s theatre, theoretical reflections and institutional work at the Centro Cattolico Cinematografico. In particular, the article aims to define Fabbri’s contribution to the RAI television productions "The Brothers Karamazov" (1969) and "The Demons" (1972), which represent many years of the author’s reflections on Dostoyevsky’s novels. It analyses The Brothers Karamazov in detail, in order to highlight the relationship between the screenplay, its production, and Sandro Bolchi’s direction.

A Gaussian-Mixture based stochastic framework for the interpretation of spatial heterogeneity in multimodal fields

We provide theoretical formulations enabling characterization of spatial distributions of variables (such as, e.g., conductivity/permeability, porosity, vadose zone hydraulic parameters, and reaction rates) that are typical of hydrogeological and/or geochemical scenarios associated with randomly heterogeneous geomaterials and are organized on various scales of heterogeneity. Our approach and ensuing formulations embed the joint assessment of the probability distribution of a target variable and its associated spatial increments, DY, taken between locations separated by any given distance (or lag). The spatial distribution of Y is interpreted through a bimodal Gaussian mixture model. The modes of the latter correspond to an indicator random field which is in turn related to the occurrence of different processes and/or geomaterials within the domain of observation. The distribution of each component of the mixture is governed by a given length scale driving the strength of its spatial correlation. Our model embeds within a unique theoretical framework the main traits arising in a stochastic analysis of these systems. These include (i) a slight to moderate asymmetry in the distribution of Y and (ii) the occurrence of a dominant peak and secondary peaks in the distribution of DY whose importance changes with lag together with the moments of the distribution. This causes the probability distribution of increments to scale with lag in way that is consistent with observed experimental patterns. We analyze the main features of the modeling and parameter estimation framework through a set of synthetic scenarios. We then consider two experimental datasets associated with different processes and observation scales. We start with an original dataset comprising microscale reaction rate maps taken at various observation times. These are evaluated from AFM imaging of the surface of a calcite crystal in contact with a fluid and subject to dissolution. Such recent high resolution imaging techniques are key to enhance our knowledge of the processes driving the reaction. The second dataset is a well established collection of Darcy-scale air-permeability data acquired by Tidwell and Wilson (1999) [Water Resour Res, 35, 3375-3387] on a block of volcanic tuff through minipermeameters associated with various measurement scales

Chronic Nodular Dermatosis: A Quiz

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Disorientation, self-awareness and ongoing learning: student midwives’ experiences of clinical placements in Italy

Objective: To explore student midwives’ perspectives, experiences and concerns regarding clinical placements in the Italian setting. Design: A qualitative phenomenological study was undertaken, with data collected through semi-structured interviews and diaries. Ethical approval was obtained. Data analysis was conducted using a thematic analysis approach. Setting: One university in Northern Italy including a midwifery undergraduate programme. Participants: Purposeful sample of 19 third-year student midwives. Findings: Four themes emerged from the data: a) becoming a midwife: disorientation, self-awareness and ongoing learning; b) mentor as key figure; c) practice and theory: a ‘chicken and egg’ situation; d) clinical placements: a window on the uniqueness of the midwifery profession. Student midwives reported a journey through different learning phases within clinical placements, from feeling disoriented while facing initial challenges in the first year of the course to having increasing awareness of their role in the second and third year of the programme. The phase of disorientation was mainly due to not being aware of the theoretical evidence behind practice, not feeling part of the team, not knowing what their role was and lack of appropriate supervision from mentors. A positive relationship with the mentor encouraged students to share perspectives and doubts, stimulating a problem solving approach. The students found it helpful when the mentor involved them in the decision making and praised them when they deserved it. A good rapport with the midwife was reported by the participants as inspiring self-confidence and cognitive enquiries; it also allowed the students to feel part of the multidisciplinary team. An overall sense of ongoing learning was still present at the end of the midwifery programme. Key conclusions and implications for practice: Continuity of mentorship and mentors’ commitment to supporting students emerged as key aspects for a positive and fruitful learning experience within practice settings. Other pivotal elements to be considered by mentors are making the students feel welcome and part of the team; orienting them on the first day of placement; allowing some time for familiarisation with the placement area and clinical policies; involving the students in the decision-making process and care planning/implementation/ evaluation. Appropriate national mandatory training should be put in place for mentors to allow a more effective learning experience in practice settings for student midwives

Un askos tra miniatura e realtà in contesto a Tarquinia

New evidence from a sealed context in Tarquinia (mid-II century B.C.) of an askos belonging to the Ruvfies Group with atranes stamp allows some observations with regard to the use of sigma instead of the usual san. The Southern connotation of the writing stands out within the known record that traditionally locates the production of such askoi in the Northern Etruscan region (Perugia), based on onomastic and epigraphic analyses. Such epigraphic evidence opens up to new speculations regarding the relationship between production and commission and the different production methods from the various artisan workshops.Una nuova attestazione di un askos del Ruvfies Group con bollo atranes a Tarquinia, in un contesto chiuso databile alla metà del II sec. a.C., consente considerazioni di natura epigrafica per la desinenza in sigma invece che in san del caso obliquo, come finora era stato sempre attestato. La caratterizzazione meridionale della grafia offre un elemento di novità all’interno del panorama conosciuto, in quanto contrasta con la tradizionale collocazione dell'officina in ambiente settentrionale (Perugia) ottenuta in base a considerazioni onomastiche ed epigrafiche. Questa evidenza epigrafica apre nuovi scenari sul rapporto fra produzione e committenza e sui modi di produzione delle botteghe artigiane

COVID-19–related skin manifestations: Update on therapy

An increasing body of evidence has been produced in a very limited period to improve the understanding of skin involvement in the current coronavirus 2019 disease pandemic, and how this novel disease affects the management of dermatologic patients. A little explored area is represented by the therapeutic approach adopted for the different skin manifestations associated with the infection. An overview of the current scenario is provided, through review of the English-language literature published until October 30, 2020, and comparison with the personal experience of the authors. As dermatologists, our primary aim is to support patients with the highest standard of care and relieve suffering, even with lesions not life-threatening. With asymptomatic COVID-19 patients, patient discomfort related to skin lesions should not be undervalued and intervention to accelerate healing should be provided. Consensus protocols are warranted to assess the best skin-targeted treatments in COVID-19 patients